Halade Ganesh V, Dorbane Anela, Ingle Kevin A, Kain Vasundhara, Schmitter Jean-Marie, Rhourri-Frih Boutayna
Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, 703 19th Street South, MC7755, Birmingham, AL, 35294, USA.
Chimie et Biologie des Membranes et Nanoobjets, University of Bordeaux, CNRS UMR 5248, 146, rue Léo Saignat, 33076, Bordeaux, France.
Anal Bioanal Chem. 2018 Mar;410(7):1965-1976. doi: 10.1007/s00216-018-0863-7. Epub 2018 Feb 6.
Myocardial infarction (MI) and subsequent progressive heart failure pathology is the major cause of death worldwide; however, the mechanism of this pathology remains unclear. The present work aimed at testing the hypothesis whether the inflammatory response is superimposed with the formation of bioactive lipid resolving molecules at the site of the injured myocardium in acute heart failure pathology post-MI. In this view, we used a robust permanent coronary ligation model to induce MI, leading to decreased contractility index with marked wall thinning and necrosis of the infarcted left ventricle. Then, we applied mass spectrometry imaging (MSI) in positive and negative ionization modes to characterize the spatial distribution of left ventricle lipids in the infarcted myocardium post-MI. After micro-extraction, liquid chromatography coupled to tandem mass spectrometry was used to confirm the structures of the imaged lipids. Statistical tools such as principal component analysis were used to establish a comprehensive visualization of lipid profile changes in MI and no-MI hearts. Resolving bioactive molecules such as resolvin (Rv) D1, RvD5, RvE3, 17-HDHA, LXA, and 18-HEPE were detected in negative ion mode MSI, whereas phosphatidyl cholines (PC) and oxidized derivatives thereof were detected in positive ion mode. MSI-based analysis demonstrated a significant increase in resolvin bioactive lipids with comprehensive lipid remodeling at the site of infarction. These results clearly indicate that infarcted myocardium is the primary location of inflammation-resolution pathomechanics which is critical for resolution of inflammation and heart failure pathophysiology. Graphical abstract Applied scheme to determine comprehensive lipidomics in failing and non-failing heart.
心肌梗死（MI）及随后进展性心力衰竭病理是全球范围内主要的死亡原因；然而，这种病理机制仍不清楚。本研究旨在验证在急性心力衰竭病理（心肌梗死后）中，炎症反应是否与损伤心肌部位生物活性脂质分解分子的形成同时存在这一假设。基于此观点，我们使用了一种可靠的永久性冠状动脉结扎模型来诱导心肌梗死，导致梗死左心室的收缩性指数降低，伴有明显的室壁变薄和坏死。然后，我们采用正离子和负离子模式的质谱成像（MSI）来表征心肌梗死后梗死心肌中左心室脂质的空间分布。经过微萃取后，液相色谱-串联质谱用于确认成像脂质的结构。使用主成分分析等统计工具来全面直观地呈现心肌梗死和非心肌梗死心脏中脂质谱的变化。在负离子模式的MSI中检测到了分解素（Rv）D1、RvD5、RvE3、17-羟基二十二碳六烯酸（17-HDHA）、脂氧素A（LXA）和18-羟基二十碳五烯酸（18-HEPE）等具有分解作用的生物活性分子，而在正离子模式中检测到了磷脂酰胆碱（PC）及其氧化衍生物。基于MSI的分析表明，在梗死部位，具有分解作用的生物活性脂质显著增加，同时伴有全面的脂质重塑。这些结果清楚地表明，梗死心肌是炎症消退病理机制的主要部位，这对于炎症消退和心力衰竭病理生理学至关重要。图摘要确定衰竭和非衰竭心脏综合脂质组学的应用方案。
